Ideal doseIdeal dose of proteinof protein substitute substitute intake intake

What do protein What do protein substitues dosubstitues do?

provide 21 amino provide 21 amino acidsacids

help growth help growth

lower phenylalanine lower phenylalanine levelslevels

some provide some provide vitamins and mineralsvitamins and minerals

How much do How much do we we give?give?

School of Thought School of Thought 11

UK advocate generous quantities of protein substitute

School of Thought School of Thought 22

children with PKU don’t need big doses of protein substitute

AimAimTo investigate if a To investigate if a lower dose of lower dose of protein substitute protein substitute can achieve can achieve the same or the same or better better control when control when compared to the compared to the dosage recommended dosage recommended by the UK by the UK

Who did we study?

25 children25 children

2-10y (median 6y)2-10y (median 6y)

13 girls; 12 boys13 girls; 12 boys

dietary treatment:dietary treatment:

- 5.5 x 50 mg phenylalanine exchanges- 5.5 x 50 mg phenylalanine exchanges

- median protein equivalent intake: 2.2 - median protein equivalent intake: 2.2 g/kg/day g/kg/day

Dosages of protein Dosages of protein substitutesubstitute

High doseHigh dose

- 2 g/kg/day - 2 g/kg/day protein protein

equivalent equivalent

Low doseLow dose

- 1.2 g/kg/day protein equivalent - 1.2 g/kg/day protein equivalent

Week 1

Week 2

Week 3

Week 4

Week 5

Week 6

Week 7

7 week study

Week 1

ControlControl

normal dose of protein substitute

Week 1 ControlControl

5 6 7

morning

night

day

Week 2 and 3

High

Week 2 and 3

High Low

Week 3

1 2 3 4 5 6 7day

Morning

Night

Weighed food record

Week 4 and 5

ControlControl

normal dose of protein substitute

Week 5 ControlControl

5 6 7

morning

night

Week 6 and 7

High Low

Week 7

1 2 3 4 5 6 7day

Morning

Night

Same food menu as week 3

Subject 1Subject 1 girl 5y girl 5y 5½exchanges 5½exchanges

Subject 2Subject 2 girl 6ygirl 6y 6 exchanges6 exchanges

Subject 3Subject 3 girl 7 ygirl 7 y 7 exchanges7 exchanges

Change in morning bloodChange in morning bloodphenylalanine concentrationsphenylalanine concentrations

T IME O F D AY

p.m.a.m

CH

AN

GE

IN P

HE

NY

LALA

NIN

E F

RO

M C

ON

TR

OL

1000

800

600

400

200

0

-200

-400

LOW DOSE

HIGH DOSE

p < 0.001 n .s .p < 0.001 n .s .

Median change in blood phenylalanine concentrations

a.m. p.m.

What are the reasons for What are the reasons for differences in change in differences in change in

blood phe levels?blood phe levels?

age: age: no correlationno correlationexchanges: exchanges: no correlationno correlationPKU mutations PKU mutations calorie intakecalorie intake

What are the reasons for What are the reasons for differences in change in differences in change in

blood phe levels?blood phe levels?

age: age: no correlationno correlationexchanges: exchanges: no correlationno correlationPKU mutations: PKU mutations: coming coming

soonsooncalorie intakecalorie intake

Reduction in calorie intakeReduction in calorie intake

SummarySummarylower dosages of protein substitute increased lower dosages of protein substitute increased

plasma phenylalanine concentrationsplasma phenylalanine concentrations

in some children, it led to very poor phe in some children, it led to very poor phe controlcontrol

individual differences may be due to severity individual differences may be due to severity of PKUof PKU

calories contributed by protein substitute is calories contributed by protein substitute is important important

BenefitsBenefitsUKUKevidence to justify dosage of

protein substitute givenimportant to justify prescription

costsNone UK countriesshould help improve dietary

control